Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development.
Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development.
复制标题
DOI：
10.1016/j.celrep.2015.12.050
复制
发表时间：
2016-01-26
期刊：
影响因子：
8.8
通讯作者：
Khokha MK
中科院分区：
文献类型：
--
作者：
Owens NDL;Blitz IL;Lane MA;Patrushev I;Overton JD;Gilchrist MJ;Cho KWY;Khokha MK
转录调控对细胞功能至关重要，调控不当可导致疾病。尽管技术调查转录组，我们缺乏一个全面的了解转录动力学，这限制了定量生物学。这是胚胎发育中的一个严峻挑战，基因表达的快速变化决定了细胞的命运。通过对非洲爪蟾胚胎的超高频采样和序列reads的绝对归一化，我们在绝对转录物数量上呈现出平滑的基因表达轨迹。在大约人类妊娠前8周的发育期间，转录动力学变化了8个数量级。通过对基因的表达动态进行排序，我们发现时间同步表达可以预测共同基因的功能。值得注意的是，单个参数，即特征时间标度，可以对转录物动力学进行全局分类，并将调节发育的基因与参与细胞代谢的基因区分开来。总的来说，我们的分析为母体和胚胎转录本的重组提供了前所未有的见解，并重新定义了我们进行定量生物学的能力。
Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development where rapid changes in gene expression dictate cell fate decisions. By ultra-high frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by 8 orders of magnitude. Ordering genes by expression dynamics, we find temporal synexpression predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.